The present invention provides the use, as Aldose Reductase Inhibitors (ARIs), for the manufacture of a medicament for the treatment and/or prevention of diabetic complications, of a compound represented by the following general formula (A) 
wherein at least one of Y or Yxe2x80x2 is OH and the others Y and Yxe2x80x2 are independently selected from the group consisting of hydrogen, halogen, hydroxy, methoxy, and nitro; X is selected from the group consisting of O, S, and ketone, or both substituted benzyl groups are directly linked as a substituted biphenyl compound.
In addition, these aldose reductase inhibitors can form salts with a pharmaceutically acceptable cation, all such salts are within the scope of this invention.
In addition, some of the compounds of this invention can form hydrates or solvates and they are also within the scope of the invention.
The present invention also provides six novel synthetic compounds having the following formula: 
The present invention is directed to novel pharmaceutical compositions, which possess Aldose Reductase inhibitory activity, and are useful for the treatment and/or prevention of diabetic complications; the present invention is also directed to novel compounds which possess Aldose Reductase inhibitory activity.
Diabetic neuropathy, diabetic cataract and retinopathy, diabetic corneal keratopathy, diabetic nephropathy, diabetic dermopathy and other diabetic microangiopathy have been known as chronic diseases as a result of diabetes which are difficult to treat. Accumulation of intracellular sorbitol, the reduced product of glucose, catalyzed by Aldose Reductase (AR) (EC 1.1.1.21), is thought to be the cause of the development of these diabetic complications1-3. Accordingly, agents for inhibiting this Aldose Reductase have been thought to be effective for the therapy and the prevention of diabetic complications and have been studied4-6. However, despite numerous attempts over 16 years, the results of aldose reductase inhibitor (ARI) trials, with the known aldose reductase inhibitors, for the treatment of diabetic complications have not proven efficacy7; also, despite the apparent structural diversity of aldose reductase inhibitors (ARIs), certain common electronic and steric features have become apparent through computer modeling, molecular orbital calculations, and known structure-activity relationships, and from competition studies using different aldose reductase inhibitors (ARIs) also suggest that ARIs interact at a single common site on the enzymes8-10.
Under these circumstances, the inventors have conducted a study looking for new compounds structurally different of the known aldose reductase inhibitors (ARIs). As a result, the present invention provides a novel class of aldose reductase inhibitors (ARIs) having the general formula (A). These compounds exhibit an excellent inhibitory activity to Aldose Reductase.
Compounds having the general formula (A) have long been known as antiseptic and antimicrobial agents11, as cardiac agents12, as antiinflammatory agents13, and as inhibitors of the enzymes: protein kinase C (PKC), protein tyrosine kinase (PTK), inosine monophosphate dehydrogenase (IMPDH), guanosine monophosphate synthetase (GMPS), and 15-lipoxygenase (15-LO)14.
Compounds having the general formula (A) have long been reported from marine sources14-18.
The present invention provides the use, as inhibitors of Aldose Reductase, for the manufacture of a medicament for the treatment and prevention of diabetic complications, of a compound represented by the following general formula (A) 
wherein at least one of Y or Yxe2x80x2 is OH and the other Y and Yxe2x80x2 are independently selected from the group consisting of hydrogen, halogen, hydroxy, methoxy, and nitro; X is selected from the group consisting of O, S, and ketone, or both subtituted benzyl groups are directly linked as a subtituted biphenyl compound.
In addition, these aldose reductase inhibitors can form salts with a pharmaceutically acceptable cation, all such salts are within the scope of this invention.
In addition, some of the compounds of this invention can form hydrates or solvates and they are also within the scope of the invention.
The present invention further provides pharmaceutical compositions which contain as active ingredient a compound with the formula (A). Examples of pharmaceutical compositions include any solid (tablets, pills, capsules, granules, etc.) or liquid (solutions, suspensions or emulsions) with suitable formulation of oral, topical or parenteral administration, and they may contain the pure compound or in combination with any carrier or other pharmacologically active compounds. These compositions may need to be sterile when administered parenterally.
The correct dosage of a pharmaceutical composition comprising compounds with the formula (A), will vary according to the pharmaceutical formulation, the mode of application, and the particular situs, host and diabetic complication being treated. Other factors like age, body weight, sex, diet, time of administration, rate of excretion, condition of the host, drug combinations, reaction sensitivities and severity of the disease shall be taken into account. Administration can be carried out continuously or periodically within the maximum tolerated dose.
The present invention also provides six novel synthetic compounds having the following formula: 
as well as a process for their preparation.